1. Field of the Invention
The invention relates to a porous, composite matrix formed from a hyaluronic acid derivative and hydrolyzed collagen, which is used as a biocompatible and biodegradable composite matrix for the repair of muculoskeletal defects.
2. Description of the Related Art
For the regeneration of tissue defects, it is necessary to use a body-compatible, slowly biodegradable matrix which under suitable conditions makes possible the differentiation of introduced cells with marked production of a specific intercellular matrix. Various matrices of this type are known in the prior art.
WO 97/28192 discloses a process for the preparation of prion-free collagen products which can be used as a spongy implant. For ocular applications, the collagen product can be crosslinked with 5% by weight hyaluronic acid to increase the transparency. The hyaluronic acid additionally stimulates the cell infiltration into the implant.
WO 91/18553 and WO 91/16857 and also U.S. Pat. No. 4,830,429 disclose composite matrices formed from collagen and up to 25% by weight of glycosaminoglycans such as hyaluronic acid.
EP-A-0 784 985 discloses a porous composite article which comprises a bioabsorbable hydrophilic material selected from gelatin, hyaluronic acid and a hyaluronic acid derivative. To avoid premature absorption, the article is additionally provided with a polymer layer which is absorbed in a delayed manner.
WO 97/14376 discloses a bone transplant matrix formed from collagen, which can contain hyaluronic acid as a birding agent.
U.S. Pat No. 5,676,964 discloses inter- and intramolecularly crosslinked esters of acidic polysaccharides such as God preferably hyaluronic acid. These esters can be employed as biodegradable, for example spongy, materials as surgical articles.
The known matrices, however, show marked restrictions in the provision of suitable medium conditions for the differentiation of introduced cells (e.g. premature absorption, unsuitable matrix composition) and are also unsatisfactory with respect to the stability necessary or handling.
An object of the present invention thus consists in making available a matrix which assists cell differentiation and intercellular matrix production and is then itself slowly degraded. Moreover, the matrix should have an adequate stability which makes the matrix highly suitable and easy to handle not only for preculture of cells in vitro but also for in-vivo implantation.
It has now been found that this object is achieved bag a composite matrix formed from a hyaluronic acid derivative and hydrolyzed collagen of specific composition.
The present invention thus relates to a porous composite matrix, the matrix being synthesized on matrix formers comprising a hyaluronic acid derivative and a hydrolyzed collagen, and the matrix formers being present in a weight ratio range of hyaluronic acid derivative to hydrolyzed collagen of 30:70 to 99:1.